Phase II clinical study of modified FOLFOX7 (intermittent oxaliplatin administration) plus bevacizumab in patients with unresectable metastatic colorectal cancer—CRAFT study
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Purpose Continuous treatment with FOLFOX therapy is associated with peripheral nerve toxicity, and to improve this inconvenient side effect various methods of administration are being investigated. A regimen of intermittent oxaliplatin administration by continuous infusion therapy, i.e., modified FOLFOX7 (mFOLFOX7) + bevacizumab, was designed with the goal of alleviating severe peripheral nerve disorders and hematological toxicity. A phase II clinical study was conducted to evaluate the efficacy and safety of this regimen. Methods Previously untreated patients were assigned to mFOLFOX7 (oxaliplatin 85 mg/m2, levofolinate [l-LV] 200 mg/m2, 5-fluorouracil [5-FU] 2400 mg/m2) + bevacizumab (5 mg/kg) administered every 2 weeks for 8 cycles, maintenance without oxaliplatin for 8 cycles, and reintroduction of mFOLFOX7 + bevacizumab for 8 cycles or until disease progression. Progression free survival (PFS) following the first dose (PFS 1) and following reintroduction of oxaliplatin (PFS 2) were used as indices for assessing the efficacy of intermittent administration. Results Fifty-two patients were enrolled, with median age of 64 years (range, 36–74). Median PFS 1 was 11.8 months (95 % confidence interval [CI], 9.5 to 13.7), median time to treatment failure was 10.3 months (95 % CI, 5.6 to 12.1), percentage of patients with neutropenia of grade 3 or higher was 7.8 %, and percentage with peripheral nerve disorders was 3.9 %. Response rate was 50 %, and 84.4 % of patients who started modified simplified LV5FU2 + bevacizumab were reintroduced to oxaliplatin. Conclusion By excluding 5-FU bolus administration and administering bevacizumab continuously the mFOLFOX7 + bevacizumab regimen with preplanned withdrawal of oxaliplatin showed high tolerability and prevented severe peripheral neuropathy and neutropenia without reducing efficacy.
KeywordsOxaliplatin Bevacizumab Stop-and-go Modified FOLFOX7 Metastatic colorectal cancer
We thank the staff and patients of the following participating institutions: Chiba Medical Center, Chiba University, Chibaken Saiseikai Narashino Hospital, Fujita Health University Hospital, Fukaya Red Cross Hospital, Kimitsu Chuo Hospital, Kumamoto University Hospital, Kurume University, Matsudo City Hospital, Minoh City Hospital, Nippon Medical School Chiba Hokusoh Hospital, Saishukan Hospital, Saitama Medical Center, Seirei Sakura Citizen Hospital, Teikyo University Chiba Medical Center, Toho University Sakura Medical Center, Tokyo Women’s Medical University, Yokoyama Gastrointestinal Hospital, and ECRIN (Epidemiological and Clinical Research Information Network) for their support.
Conflict of interest
We declare that we have no conflicts of interest.
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